A Study of Abiraterone Acetate Plus Prednisone With or Without Abemaciclib (LY2835219) in Participants With Prostate Cancer (CYCLONE 2)

A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study of Abiraterone Acetate Plus Prednisone With or Without Abemaciclib in Patients With Metastatic Castration-Resistant Prostate Cancer

This study is being done to see how safe and effective abemaciclib is when given together with abiraterone acetate plus prednisone in participants with metastatic castration resistant prostate cancer. Prednisolone may be used instead of prednisone per local regulation.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Abemaciclib; Drug: Placebo; Drug: Abiraterone Acetate; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 2; Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
    • Kogarah, New South Wales, Australia, 2228
      • Southside Cancer Care Centre
    • Macquarie University, New South Wales, Australia, 2109
      • Macquarie University
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
    • Melbourne, Victoria, Australia, 3065
      • St Vincent's hospital
• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Second Affiliated hospital of Anhui Medical University
    • Wuhu, Anhui, China, 241001
      • Wannan Medical College Yijishan Hospital
  • Gansu
    • Lanzhou, Gansu, China, 730030
      • Lanzhou University Second Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Centre
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin medical university cancer hospital
  • Henan
    • Luoyang, Henan, China, 471003
      • The First Affiliated Hospital of Henan University of Science &Technology
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wuhan Union Hospital
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital Tongji Medical,Science & Technology
  • Hunan
    • ChangSha, Hunan, China, 410005
      • Hunan Provincial People's Hospital
    • Changsha, Hunan, China, 410013
      • Hunan Cancer hospital
  • Jiangsu
    • Nantong, Jiangsu, China, 226361
      • Nantong Tumor Hospital
    • Wuxi, Jiangsu, China, 214023
      • Wuxi People's Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of NanChang University
  • Jilin
    • Changchun, Jilin, China, 130021
      • Jilin Province People's Hospital
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Shandong
    • Yantai, Shandong, China, 264099
      • Yantai Yuhuangding Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital Affiliated Fudan University
  • Sichuan
    • Nanchong, Sichuan, China, 637000
      • Nanchong Central Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
    • Tianjin, Tianjin, China, 300211
      • The Second Hospital of Tianjin Medical University
  • Xinjiang
    • Urumqi, Xinjiang, China, 830000
      • Xinjiang Medical University Cancer Hospital - Urumqi
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University
    • Ningbo, Zhejiang, China, 315010
      • Ningbo First Hospital
• Denmark
  • Hovedstaden
    • Copenhagen, Hovedstaden, Denmark, 2100
      • Rigshospitalet
  • Sjælland
    • Næstved, Sjælland, Denmark, 4700
      • Næstved Sygehus
• France
  • Bordeaux, France, 33075
    • CHU de Bordeaux Hop St ANDRE
  • Languedoc-Roussillon
    • Montpellier, Languedoc-Roussillon, France, 34070
      • Centre de Cancerologie du Grand Montpellier
  • Pays-de-la-Loire
    • Le Mans, Pays-de-la-Loire, France, 72000
      • Clinique Victor Hugo Le Mans
  • Rhône-Alpes
    • Lyon CEDEX 08, Rhône-Alpes, France, 69373
      • Centre Leon Berard
  • Vendée
    • La Roche-sur-Yon, Vendée, France, 85000
      • CHD Vendée
  • Île-de-France
    • Créteil, Île-de-France, France
      • Christophe TOURNIGAND
• Germany
  • Baden-Württemberg
    • Nürtingen, Baden-Württemberg, Germany, 72622
      • Studienpraxis Urologie
    • Tübingen, Baden-Württemberg, Germany, 72076
      • Universitaetsklinikum Tuebingen
  • Niedersachsen
    • Holzminden, Niedersachsen, Germany, 37603
      • Gesundheitszentrum Holzminden
  • Nordrhein-Westfalen
    • Cologne, Nordrhein-Westfalen, Germany, 50968
      • Studienzentrum Bayenthal Urologische Partnerschaft Köln
    • Mettmann, Nordrhein-Westfalen, Germany, 40822
      • Urologie Neandertal - Praxis Mettmann
    • Münster, Nordrhein-Westfalen, Germany, 48149
      • Universitätsklinikum Münster - Albert Schweitzer Campus
    • Wesel, Nordrhein-Westfalen, Germany, 46483
      • Private Practice - Dr. Stammel & Dr. Garcia
  • Sachsen
    • Leipzig, Sachsen, Germany, 4105
      • Private Practice - Dr. Silvio Szymula
  • Sachsen-Anhalt
    • Lutherstadt Eisleben, Sachsen-Anhalt, Germany, 06295
      • Private Practice - Dr. Ralf Eckert
• Japan
  • Gifu, Japan, 501-1112
    • Gifu University Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Aichi
    • Nagoya, Aichi, Japan, 466-8650
      • Japanese Red Cross Nagoya Daini Hospital
  • Aomori
    • Hirosaki, Aomori, Japan, 036-8563
      • Hirosaki University Hospital
  • Chiba
    • Sakura, Chiba, Japan, 285-0841
      • Toho University Sakura Medical Center
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 232-0024
      • Yokohama City University Medical Center
  • Saitama
    • Ina-machi, Saitama, Japan, 362-0806
      • Saitama Prefectural Cancer Center
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 431-3192
      • Hamamatsu University Hospital
  • Tokyo
    • Shinagawa, Tokyo, Japan, 142-8555
      • Showa University Hospital
• Korea, Republic of
  • Seoul-teukbyeolsi [Seoul]
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 3080
      • Seoul National University Hospital
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 6351
      • Samsung Medical Center
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 3722
      • Severance Hospital, Yonsei University Health System
    • Songpagu, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 5505
      • Asan Medical Center
• Netherlands
  • Utrecht, Netherlands, 3543 AZ
    • St. Antonius Ziekenhuis, locatie Utrecht
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6532 SZ
      • Canisius-Wilhelmina Ziekenhuis
• Romania
  • București, Romania, 31422
    • Gral Medical Diagnostic Center
  • Constanța
    • Ovidiu, Constanța, Romania, 905900
      • Ovidius Clinical Hospital OCH
  • Dolj
    • Craiova, Dolj, Romania, 200542
      • Centrul de Oncologie "Sfântul Nectarie"
• Spain
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 8035
      • Hospital Universitari Vall d'Hebron
    • Hospitalet, Barcelona [Barcelona], Spain, 8907
      • Instituto Catalan de Oncologia - Hospital Duran i Reynals
  • Catalunya [Cataluña]
    • Barcelona, Catalunya [Cataluña], Spain, 8036
      • Hospital Clínic de Barcelona
  • Madrid, Comunidad De
    • Madrid, Madrid, Comunidad De, Spain, 28041
      • Hospital Universitario 12 de octubre
  • Málaga
    • Malaga, Málaga, Spain, 29010
      • Hospital Universitario Virgen de la Victoria
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • St. Joseph's Hospital and Medical Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic in Arizona - Phoenix
    • Tucson, Arizona, United States, 85719
      • The University of Arizona Cancer Center - North Campus
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • St. Bernards Medical Center
  • California
    • Bakersfield, California, United States, 93309
      • CBCC Global Research, Inc.
    • Fullerton, California, United States, 92835
      • St. Jude Medical Center
    • La Jolla, California, United States, 92093
      • Moores Cancer Center
    • Los Angeles, California, United States, 90095
      • UCLA Hematology/Oncology - Westwood (Building 100)
    • Los Angeles, California, United States, 90024
      • TRIO-US (Translational Research in Oncology-US)
    • Monterey, California, United States, 93940
      • Pacific Cancer Care
    • Santa Barbara, California, United States, 93105
      • Sansum Clinic_Kendle
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Center
  • Florida
    • Hollywood, Florida, United States, 33024
      • Millennium Oncology - Hollywood
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology And Hematology at Parkview Comprehensive Cancer Center
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology - Columbia
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • M Health Fairview University of Minnesota Medical Center - East Bank
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Comprehensive Cancer Centers of Nevada
  • New York
    • Albany, New York, United States, 12206
      • New York Oncology Hematology (NYOH) - Clifton Park Cancer Center
    • Syracuse, New York, United States, 13210
      • Associated Medical Professionals - Urology
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Medical Center
  • Texas
    • Temple, Texas, United States, 76508
      • Baylor Scott & White Medical Center - Temple
    • The Woodlands, Texas, United States, 77380
      • US Oncology
    • The Woodlands, Texas, United States, 77380
      • Northwest Cancer Specialists PC
    • The Woodlands, Texas, United States, 77380
      • Texas Oncology - Longview Cancer Center
    • The Woodlands, Texas, United States, 77380
      • Texas Oncology Cancer Care and Research Center
    • The Woodlands, Texas, United States, 77380
      • Texas Oncology Fort Worth
    • The Woodlands, Texas, United States, 77380
      • Texas Oncology-Memorial City
    • The Woodlands, Texas, United States, 77380
      • USO-Cancer Care Center of Brevard, Inc.
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Vermont
    • Burlington, Vermont, United States, 05405
      • The University of Vermont Medical Center Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate.
• Metastatic prostate cancer documented by positive bone scan and/or measurable soft tissue metastatic lesions by CT or magnetic resonance imaging (MRI).

• Progressive disease at study entry demonstrated during continuous androgen-deprivation therapy (ADT)/post orchiectomy defined as one or more of the following:

  • PSA progression
  • Radiographic progression per Response Evaluation Criteria in Solid Tumors (RECIST)1.1 for soft tissue and/or per Prostate Cancer Working Group 3 (PCWG3) for bone, with or without PSA progression
• Have adequate organ function.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

Exclusion Criteria:

• Prior therapy with cytochrome P450 (CYP)17 inhibitors.
• Prior treatment with abemaciclib or any cyclin-dependent kinase (CDK) 4 & 6 inhibitors.
• Prior cytotoxic chemotherapy for metastatic castration resistant prostate cancer (participants treated with docetaxel in the metastatic hormone-sensitive prostate cancer [mHSPC] are eligible). Prior radiopharmaceuticals for prostate cancer, or prior enzalutamide, apalutamide, darolutamide or sipuleucel-T. Participants who had prior radiation or surgery to all target lesions.
• Currently enrolled in a clinical study involving an investigational product.
• Gastrointestinal disorder affecting the absorption or ability to swallow large pills.
• Clinically significant heart disease, active or chronic liver disease, moderate/severe hepatic impairment (Child-Pugh Class B and C).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A1. Abiraterone plus Prednisone and Abemaciclib; Abiraterone plus prednisone administered orally and abemaciclib administered orally.	Drug: Abemaciclib; Administered orally.; Other Names: LY2835219; Drug: Abiraterone Acetate; Administered orally.; Drug: Prednisone; Administered orally.
Experimental: A2. Abiraterone plus Prednisone and Abemaciclib; Abiraterone plus prednisone administered orally and abemaciclib administered orally.	Drug: Abemaciclib; Administered orally.; Other Names: LY2835219; Drug: Abiraterone Acetate; Administered orally.; Drug: Prednisone; Administered orally.
Active Comparator: B1. Abiraterone plus Prednisone and Placebo; Abiraterone plus prednisone administered orally and placebo administered orally.	Drug: Placebo; Administered orally.; Drug: Abiraterone Acetate; Administered orally.; Drug: Prednisone; Administered orally.
Active Comparator: B2. Abiraterone plus Prednisone and Placebo; Abiraterone plus prednisone administered orally and placebo administered orally.	Drug: Placebo; Administered orally.; Drug: Abiraterone Acetate; Administered orally.; Drug: Prednisone; Administered orally.
Experimental: A. Abiraterone plus Prednisone and Abemaciclib; Abiraterone plus prednisone administered orally and abemaciclib administered orally.	Drug: Abemaciclib; Administered orally.; Other Names: LY2835219; Drug: Abiraterone Acetate; Administered orally.; Drug: Prednisone; Administered orally.
Active Comparator: B. Abiraterone plus Prednisone and Placebo; Abiraterone plus prednisone administered orally and placebo administered orally.	Drug: Placebo; Administered orally.; Drug: Abiraterone Acetate; Administered orally.; Drug: Prednisone; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Progression Free Survival (rPFS)	rPFS by investigator assessment	Baseline to Radiographic Disease Progression or Death from Any Cause (Estimated up to 21 Months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Prostate-Specific Antigen (PSA) Progression	Time to PSA progression	Baseline to the Date of the First Observation of PSA Progression (Estimated up to 21 Months)
Radiographic Progression Free Survival (rPFS)	rPFS by blinded, independent, central review	Baseline to Radiographic Disease Progression or Death from Any Cause (Estimated up to 21 Months)
Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR)	ORR: Percentage of participants with a CR or PR	Baseline to Radiographic Disease Progression (Estimated up to 21 Months)
Duration of Response (DOR)	DOR	Date of First Documented CR or PR to Date of Radiographic Disease Progression or Death from Any Cause (Estimated up to 21 Months)
Overall Survival (OS)	OS	Baseline to Date of Death Due to Any Cause (Estimated up to 40 Months)
Time to Symptomatic Progression	Time to symptomatic progression	Baseline to the Date of the First Documented Symptomatic Progression (Estimated up to 21 Months)
Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib	PK: Mean steady state exposure of abemaciclib	Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles)
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567	PK: Mean steady state exposure of abemaciclib metabolite LSN2839567	Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles)
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726	PK: Mean steady state exposure of abemaciclib metabolite LSN3106726	Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles)
PK: Mean Steady State Exposure of Abiraterone Acetate	PK: Mean Steady State Exposure of Abiraterone Acetate	Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles)
Time to Worst Pain Progression	Measured by the Worst Pain Numeric Rating Scale (NRS) and World Health Organization-Analgesic Ladder (WHO-AL). NRS score measures worst pain over the last 24 hours on a 0 to 10-point NRS, where 0 -s "no pain" and 10 is "pain as bad as you can imagine. The WHO-AL classifies analgesic use into four categories, where 1 = no analgesic and 4 = strong opioids.	Baseline through follow-up (Estimated up to 21 months)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of Abiraterone Acetate Plus Prednisone With or Without Abemaciclib (LY2835219) in Participants With Prostate Cancer

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2018
• Primary Completion (Actual): January 2, 2024
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: September 18, 2018
• First Submitted That Met QC Criteria: October 11, 2018
• First Posted (Actual): October 16, 2018

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: mCRPC; Metastatic Castration Resistant Prostate Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Prednisone; Abiraterone Acetate
• Other Study ID Numbers: 16598; I3Y-MC-JPCM (Other Identifier: Eli Lilly and Company); 2016-004276-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No